Differential in vitro neurotoxicity of the flame retardant PBDE-99 and of the PCB Aroclor 1254 in human astrocytoma cells

摘要: Abstract Polybrominated diphenyl ethers (PBDEs) are an important class of flame retardants. Because their presence in maternal milk and structural similarity to polychlorinated biphenyls (PCBs), concern has been raised on possible developmental neurotoxicity. Aim the present study was investigate vitro effects PBDE-99 (2,2′, 4,4′, 5-pentabromodiphenyl ether) astroglial cells (human 132-1N1 astrocytoma cells) comparing it with those PCB mixture Aroclor 1254. Both 1254 caused a concentration-dependent inhibition MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) reduction, however, only latter increased lactate dehydrogenase (LDH) release or cell death, assessed by trypan blue assay. translocation three protein kinase C (PKC) isozymes (α, ɛ, ζ) cells, while affected PKCα ɛ translocation. However, pre-incubation PKC inhibitor GF109203X down-regulation phorbol ester PMA, had minimal no effect 1254-induced cytotoxicity. Similarly, calcium chelator BAPTA-AM, tyrosine genistein, MEK (mitogen activated kinase) PD98059 cytoxicity. On other hand, phosphatidylinositol 3 (PI-3K) LY290042 enhanced toxicity, but did not affect involvement PI-3K apoptotic ability induce apoptosis investigated. PBDE-99, 1254, death TUNEL method Hoechst 33258 staining, via p53 dependent mechanism. These results suggest that exert differential cytotoxic human cells.